Brimocomb

PACKAGE LEAFLET: INFORMATION FOR

THE USER
BRIMOCOMB 2 mg/ml + 5 mg/ml eye drops, solution
Equivalent medicine (only for packages containing 1 and 3 vials of 5 ml)
Please read this leaflet carefully before using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What BRIMOCOMB is and what it is used for
2. What you need to know before using BRIMOCOMB
3. How to use BRIMOCOMB
4. Possible side effects
5. How to store BRIMOCOMB
6. Contents of the pack and other information

1. What BRIMOCOMB is and what it is used for

BRIMOCOMB is an eye drop used to control glaucoma. It contains two different active substances (brimonidine and timolol) that reduce elevated pressure inside the eye. Brimonidine belongs to a group of medicines called alpha-2 adrenergic receptor agonists. Timololo belongs to a group of medicines called beta-blockers. BRIMOCOMB is prescribed to reduce high eye pressure when beta-blocker eye drops alone are not sufficient.
The eye contains a clear aqueous fluid that helps transport nutrients within the eye. This fluid is continuously drained from the eye, and new fluid is produced to replace the drained fluid. If fluid drainage is too slow, pressure inside the eye increases and may damage vision. BRIMOCOMB works by reducing the production of fluid and increasing the amount of fluid that is drained. This reduces pressure inside the eye while maintaining the eye's nutrient transport function.

2. What you need to know before using BRIMOCOMB

Do not use BRIMOCOMB

• if you are allergic to brimonidine tartrate, timolol, beta-blockers, or any other component of this medicine (listed in section 6). Symptoms of an allergic reaction may include swelling of the face, lips, and throat, shortness of breath, feeling faint, difficulty breathing, itching, or redness around the eye
• if you have or have had breathing problems such as asthma or severe chronic obstructive pulmonary disease (COPD) (a serious lung condition that may cause shortness of breath, breathing difficulties, and/or persistent cough)
• if you have heart problems, such as slow heartbeat, heart failure, or heart rhythm disorders (unless controlled by a pacemaker)
• if you are taking monoamine oxidase inhibitors (MAO inhibitors) or certain other antidepressant medicines

BRIMOCOMB must not be used in children under 2 years of age and should generally not be used in children aged between 2 and 17 years.
If you think any of these situations may apply to you, do not use BRIMOCOMB before consulting your doctor again.

Warnings and precautions
Talk to your doctor or pharmacist before using BRIMOCOMB if you have or have previously had:

• coronary artery disease (symptoms may include chest pain or tightness, shortness of breath, or suffocation), heart failure, low blood pressure
• heart rhythm disorders, such as slow heartbeat
• breathing problems, asthma, or chronic obstructive lung disease
• poor blood circulation (such as Raynaud’s disease or Raynaud’s syndrome)
• diabetes, as timolol may mask the signs and symptoms of low blood sugar
• overactive thyroid gland, as timolol may mask the signs and symptoms
• liver or kidney problems
• a tumor of the adrenal glands
• eye surgery to reduce intraocular pressure
• any allergies (e.g., hay fever, eczema) or a history of severe allergic reactions; you should know that you may need to increase your usual dose of adrenaline used to treat a severe reaction
• Before undergoing surgery, inform your doctor that you are using BRIMOCOMB, as timolol may alter the effects of certain medicines used during anesthesia.

For athletes: using this medicine without a therapeutic need constitutes doping and may result in a positive anti-doping test.

Other medicines and BRIMOCOMB
BRIMOCOMB may affect or be affected by other medicines you are taking, including other eye drops used to treat glaucoma.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those for conditions unrelated to your eye problem, even if they do not require a prescription.

Certain medicines may interact with BRIMOCOMB, so it is particularly important to inform your doctor if you are taking:

• painkillers
• medicines to help you sleep or for anxiety
• medicines for high blood pressure (hypertension)
• medicines for heart conditions (e.g., irregular heartbeat), such as beta-blockers, digoxin, or quinidine (used to treat heart problems and some types of malaria)
• medicines for diabetes or high blood sugar levels
• medicines for depression such as fluoxetine and paroxetine
• another eye drop used to reduce high eye pressure (glaucoma)
• medicines for severe allergic reactions
• medicines affecting hormones, such as adrenaline and dopamine
• medicines acting on blood vessel muscles
• medicines for heartburn or stomach ulcers

Inform your doctor if the dose of any medicine you are currently taking has changed or if you regularly consume alcohol.
If you require anesthesia, inform your doctor or dentist that you are using BRIMOCOMB.

Pregnancy and breastfeeding
If you are pregnant, breastfeeding, suspect you may be pregnant, or are planning to become pregnant, consult your doctor or pharmacist before using this medicine.
Do not use BRIMOCOMB during pregnancy unless your doctor considers it necessary.
Do not use BRIMOCOMB while breastfeeding. Timolol may pass into breast milk. Consult your doctor before taking any medicine during breastfeeding.

Driving and using machines
In some patients, BRIMOCOMB may cause drowsiness, fatigue, or blurred vision. Do not drive or operate machinery until these symptoms have resolved. If any problems occur, inform your doctor.

BRIMOCOMB contains benzalkonium chloride
Contact lenses

• Do not use BRIMOCOMB while wearing contact lenses. Wait at least 15 minutes after administering BRIMOCOMB before reinserting your contact lenses.
• A preservative in BRIMOCOMB (benzalkonium chloride) may cause eye irritation and is known to discolor soft contact lenses.

3. How to use BRIMOCOMB

Take this medicine exactly as directed by your doctor or pharmacist. If you have
any doubts, consult your doctor or pharmacist.
Use in children and adolescents
BRIMOCOMB must not be used in children under 2 years of age.
BRIMOCOMB is generally not recommended for use in children and adolescents (aged between 2 and 17
years).
Use in adults, including elderly people
The recommended dose is one drop of BRIMOCOMB twice daily, approximately 12 hours apart. Do not
change the dose or stop using the product without speaking to your doctor.
If you are using BRIMOCOMB with other eye drops, wait at least 5 minutes between using BRIMOCOMB and the other eye drops.
Instructions for use
Do not use the bottle if the tamper-evident seal is not intact before first use.
Wash your hands before opening the bottle. Tilt your head backwards and look upwards.

1. Gently pull down the lower eyelid to form a small pocket.
2. Invert the bottle and apply slight pressure to release one drop of eye drops into

each eye to be treated.

3. Release the lower eyelid and close the eye.
4. Keep the eye closed and press with your index finger against the corner of the eye (the side where the eye meets the nose) for two minutes. This will help prevent BRIMOCOMB from being absorbed into the rest of the body.

If the drop did not enter the eye, repeat the procedure.
To avoid contamination, the tip of the bottle must not touch the eye or any other surface. Immediately after using the medicine, close the bottle tightly by screwing the cap back on.
If you use more BRIMOCOMB than you should
Adults
If you have instilled more BRIMOCOMB than recommended, it is unlikely to cause serious consequences.
Take the next dose at the usual time. If you are concerned, consult your doctor or pharmacist.
Neonates and children
Several cases of overdose have been reported in neonates and children who used brimonidine (one of the active substances in BRIMOCOMB) as part of glaucoma treatment. Symptoms include:
drowsiness, weakness, low body temperature, pallor, and breathing difficulties. If any of these adverse effects occur, contact your doctor immediately.
Adults and children
If BRIMOCOMB has been accidentally ingested, contact your doctor immediately.
If you forget to use BRIMOCOMB
If you forget to use BRIMOCOMB, instill one drop into the affected eye as soon as you remember, then resume your regular dosing schedule. Do not use a double dose to make up for the missed dose.
If you stop using BRIMOCOMB
For BRIMOCOMB to work properly, it must be used every day.
If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
If you experience any of the following side effects, contact your doctor immediately:

• Heart failure (e.g. chest pain) or irregular heartbeat
• Increased or decreased heart rate or reduced blood pressure

The following side effects have been reported with BRIMOCOMB:

Eye disorders
Very common (may affect more than 1 in 10 people):

• Red or burning eye

Common (may affect up to 1 in 10 people):

• Stinging or pain in the eye
• Allergic reaction in the eye or skin around the eye
• Small cracks on the surface of the eye (with or without inflammation)
• Swelling, redness and inflammation of the eyelid
• Irritation or sensation of a foreign body in the eye
• Itching of the eye and eyelid
• Follicles or white spots on the transparent layer covering the surface of the eye
• Vision disturbances
• Tearing
• Dry eye
• Sticky eyes

Uncommon (may affect up to 1 in 100 people):

• Difficulty seeing clearly
• Swelling or inflammation of the transparent layer covering the surface of the eye
• Tired eyes
• Light sensitivity
• Eyelid pain
• Whitening of the transparent layer covering the surface of the eye
• Swelling or areas of inflammation under the surface of the eye
• Floating shapes in front of the eyes

Not known (frequency cannot be estimated from the available data):

• Blurred vision

General disorders
Common (may affect up to 1 in 10 people):

• High blood pressure
• Depression
• Drowsiness
• Headache
• Dry mouth
• General weakness

Uncommon (may affect up to 1 in 100 people):

• Heart failure
• Irregular heartbeat
• Dizziness
• Feeling faint
• Dry nose
• Altered taste
• Nausea
• Diarrhea

Not known (frequency cannot be estimated from the available data):

• Increased or decreased heart rate
• Low blood pressure
• Facial flushing

Some of these effects may be due to an allergy to any of the components. Additional side effects have been observed with brimonidine or timolol and may therefore also occur with BRIMOCOMB.
The following additional side effects have been observed with brimonidine:

• Inflammation inside the eye, pupil constriction, difficulty sleeping, feeling cold, shortness of breath, gastrointestinal and digestive symptoms, generalized allergic reactions, skin reactions including redness, facial swelling, itching, and dilation of blood vessels

Like other eye medicines, BRIMOCOMB (brimonidine/timololo) is absorbed into the bloodstream.
Absorption of timololo, the beta-blocking component of BRIMOCOMB, may cause side effects similar to those observed with beta-blockers administered intravenously and/or orally. The incidence of side effects following topical ophthalmic administration is lower than that following oral or injectable administration. The listed side effects include those observed with the class of beta-blockers used to treat eye diseases:

• Generalized allergic reactions, including swelling under the skin (which may occur in areas such as the face and limbs and may block the airways, causing difficulty swallowing or breathing), urticaria (itchy rash), localized and generalized skin rash, itching, sudden severe allergic reaction that may be life-threatening
• Low blood sugar levels
• Sleep disturbances (insomnia), nightmares, memory loss
• Stroke, reduced blood flow to the brain, worsening of signs and symptoms of myasthenia gravis (muscle disorders), unusual sensations (such as tingling or numbness)
• Corneal inflammation, detachment of the layer beneath the retina containing blood vessels following filtering surgery which may cause visual disturbances, decreased corneal sensitivity, corneal erosion (damage to the front layer of the eyeball), drooping of the upper eyelid (resulting in half-closure of the eye), double vision
• Chest pain, edema (fluid accumulation), changes in heart rhythm or rate, a type of cardiac arrhythmia, heart attack, heart failure
• Raynaud's phenomenon, cold hands and feet
• Constriction of the airways (especially in patients with pre-existing lung disease), breathing difficulty, cough
• Indigestion, abdominal pain, vomiting
• Hair loss, white-silver appearing skin rash (psoriasiform rash) or worsening of psoriasis, skin rash
• Muscle pain not caused by physical exercise
• Sexual dysfunction, reduced sexual desire
• Muscle weakness/fatigue

Other side effects reported with eye drops containing phosphates:
In very rare cases, some patients with severe damage to the outermost transparent layer of the eye (the cornea) have developed opaque spots on the cornea due to calcium accumulation during treatment.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.agenziafarmaco.gov.it/it/responsabili.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store BRIMOCOMB

Keep this medicine out of the sight and reach of children.
Store the bottle in the original packaging to protect the medicine from light. Do not store above 25 °C.
Use only one bottle at a time.
Do not use this medicine after the expiry date stated on the label of the bottle and on the carton after EXP. The expiry date refers to the last day of that month.
If the medicine changes colour or shows any other signs of deterioration, consult your pharmacist who will advise you what to do.
You must discard the bottle four weeks after first opening, even if there are still drops remaining. This will help prevent infections. To help you remember, write the date of opening in the space provided on the box.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What BRIMOCOMB contains
The active substances are brimonidine tartrate and timolol.
One ml of solution contains 2 mg of brimonidine tartrate and timolol maleate equivalent to 5 mg of
timolol.
The other components are: benzalkonium chloride (a preservative), monosodium phosphate monohydrate,
disodium phosphate heptahydrate and purified water.
Small amounts of hydrochloric acid or sodium hydroxide may be added to adjust the solution to the correct pH (a measure of the acidity or alkalinity of the solution).

Description of the appearance of BRIMOCOMB and contents of the pack
BRIMOCOMB is a clear yellowish-green coloured eye drop solution supplied in a pack containing 1, 3 or 6 plastic bottles, each with a cap. Each bottle contains 5 ml of solution.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
DOC Generici Srl
Via Turati 40
20121 Milano
Italy

Manufacturer
Combino Pharm (Malta) Ltd.
HF 60 Hal Far Industrial Estate
Hal Far BBG 3000
Malta

This medicinal product is authorised in the European Economic Area countries under the following names:
Denmark: Brimonidintartrat/Timolol DOC Generici øjendråber, opløsning
Italy: BRIMOCOMB